Notch信号通路对人胰腺癌细胞NF-KB活性和侵袭能力的影响  

Effect of Notch Signaling Pathway on NF-kB Activation and Invasiveness of Human Pancreatic Cancer Cells

作　　者：史薇[1] 辜金莲[1] 曾峥[1] 李莉莉[1] 黎钟燕[1] 李洁[1] 陈蕴贤[1] 冯凯瑜[1] 莫少芬[1] 

机构地区：[1]广州市第一人民医院老年病科,510180

出　　处：《胃肠病学》2012年第7期413-416,共4页Chinese Journal of Gastroenterology

基　　金：2012年广州市医药卫生科技项目(20121A011008)资助

摘　　要：背景:Notch信号通路在多种人类恶性肿瘤的发生、发展中起关键作用。研究显示Notch与NF-κB信号通路之间的交互作用可促进胰腺癌进展。目的:明确Notch信号通路对胰腺癌侵袭性的影响及其可能机制。方法:体外培养人胰腺癌细胞株BxPC3,以Notch-1 siRNA下调其Notch-1表达,同时设置转染对照siRNA的阴性对照组和不予siRNA干扰的空白对照组。以Transwell细胞侵袭实验观察各组BxPC3细胞的侵袭能力,电泳迁移率变动分析(EMSA)检测NF-κB活性,蛋白质印迹法检测Notch-1、NF-κB P65、血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)蛋白表达。结果:经Notch-1 siRNA干扰、Notch-1表达下调的BxPC3细胞,Transwell细胞侵袭实验穿膜细胞数较空白对照组和阴性对照组显著减少(26.5±1.3对78.5±2.4和76.7±2.2,P<0.01),NF-κB活性显著降低(P<0.01),NF-κB p65、VEGF、MMP-9蛋白表达显著下调(P<0.05)。结论:Notch-1可通过激活NF-κB促进其下游基因VEGF、MMP-9表达,由此增强胰腺癌的侵袭性。Background： Notch signaling pathway plays a critical role in the pathogenesis and progression of various human malignancies. It has been demonstrated that crosstalk between Notch and NF-κB signaling pathways promotes pancreatic cancer progression. Aims ： To study the effect of Notch signaling pathway on invasion of pancreatic cancer and its possible mechanism. Methods： Human pancreatic cancer cell line BxPC3 was cultured in vitro and transfected with Notch-1 siRNA to down-regulate Notch-1 expression. BxPC3 cells transfected with controlled siRNA served as negative controls and those without siRNA interference served as blank controls. Invasive capacity of BxPC3 cells was assessed by Transwell cell invasion assay. NF-κB activity and the protein expressions of Notch-1, NF-κB p65, vascular endothelial growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） were determined by electrophoretic mobility shift assay （EMSA） and Western blotting, respectively. Results： Expression of Notch-1 in BxPC3 cells was significantly inhibited by siRNA interference. Compared with blank control group and negative control group, the number of penetrating cells in Transwell cell invasion assay was significantly reduced in Notch-1 siRNA transfected BxPC3 cells （26.5 ± 1.3 vs. 78.5 ± 2.4 and 76.7 ± 2.2, P 〈 0.01 ） ; the NF-κB activity, as well as the protein expressions of NF-κB p65, VEGF and MMP-9 in Notch-1 siRNA transfected group were also decreased significantly （P 〈 0.05）. Conclusions：Notch-1 may activate NF-κB and subsequently up-regulate its target genes, such as VEGF and MMP-9 expressions, resulting in pancreatic cancer invasion.

关 键 词：胰腺肿瘤 肿瘤侵润 受体 Notchl RNA干扰 NF-KB 血管内皮生长因子类 基质金属蛋白酶9 

分 类 号：R735.9[医药卫生—肿瘤]